Type 1 Diabetes
Conditions
Brief summary
The primary aim of this pilot study is to test whether gluten-free diet (GFD) instituted in children shortly after onset of Type 1 Diabetes (T1D) can decelerate the decline in beta cell function as compared to age matched controls. Primary objective of the trial is the change in C-peptide area under the curve measured by mixed-meal tolerance test (MMTT) between group on GFD and standard gluten-containing diet. Secondary objectives are: * Changes in immune parameters between gluten-free diet group and control group; * Differences in fecal microbiome between children on normal diet and children on GFD;
Interventions
OTHERGluten-free diet
Sponsors
Faculty Hospital Kralovske Vinohrady
Czech Academy of Sciences
University Hospital, Motol
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 19 Years
Healthy volunteers
No
Inclusion criteria
* Type 1 Diabetes (T1D) diagnosed according to the American Diabetes Association criteria
Exclusion criteria
* negativity of the three diabetes-related autoantibodies at T1D onset; * negativity of celiac-disease high risk Human Leucocyte Antigen DQB1 (HLA-DQB1) and Human Leucocyte Antigen DQA1 (HLA-DQA1) genotype HLA-DQB1\*03:02-DQA1\*03 nor DQB1\*02-DQA1\*05 molecules; * celiac disease or positive transglutaminase antibody test; * body mass index over two standard deviations of the age and height standard; * any concomitant disease potentially influencing immune response or gluten sensitivity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in C-peptide Area Under the Curve Measured by Mixed-meal Tolerance Test (MMTT) Between Group on GFD and Standard Gluten-containing Diet. | Month 1 (baseline) - Month 12 (end of intervention) | Area under the curve of C-peptide in MMT test at 0, 30, 60, 90 and 120 minutes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Mean HbA1c at 6 and 12 Months Relative to Baseline at Month 1. | Month 1 (baseline) - Month 6 - Month 12 (end of intervention) | — |
| Changes in Mean Insulin Dose at 6 and 12 Months Relative to Baseline at Month 1. | Month 1 (baseline) - Month 6 - Month 12 (end of intervention) | — |
| Changes in Immunological Parameters (FoxP3 Tregs, Th1 and Th17 Counts) at 12 Months Relative to Baseline at Month 1. | Month 1 (baseline) - Month 12 (end of intervention) | — |
| Differences in Fecal Microbiome Between Children on Normal Diet and Children on Gluten-free Diet Over the First Year of Diabetes Duration | Month 1 (before intervention) - Pooled values throughout the intervention (months 3-12) - Month 15 (after intervention) | Measures are shown as pooled values at all timepoints during the intervention period compared to control group throughout the same time-period. |
Countries
Czechia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gluten-free Diet Gluten-free diet for pediatric patients with type 1 diabetes | 26 |
| Conventional Diet Conventional gluten-containing diet for pediatric patients with type 1 diabetes | 19 |
| Total | 45 |
Baseline characteristics
| Characteristic | Conventional Diet | Total | Gluten-free Diet |
|---|---|---|---|
| Age, Categorical <=18 years | 19 Participants | 45 Participants | 26 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 10.1 years STANDARD_DEVIATION 3.5 | 10.2 years STANDARD_DEVIATION 3.3 | 10.7 years STANDARD_DEVIATION 3.2 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Czechia | 19 participants | 45 participants | 26 participants |
| Sex: Female, Male Female | 3 Participants | 16 Participants | 13 Participants |
| Sex: Female, Male Male | 16 Participants | 29 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 19 |
| other Total, other adverse events | 0 / 26 | 0 / 19 |
| serious Total, serious adverse events | 0 / 26 | 0 / 19 |
Outcome results
Primary
Change in C-peptide Area Under the Curve Measured by Mixed-meal Tolerance Test (MMTT) Between Group on GFD and Standard Gluten-containing Diet.
Area under the curve of C-peptide in MMT test at 0, 30, 60, 90 and 120 minutes.
Time frame: Month 1 (baseline) - Month 12 (end of intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gluten-free Diet | Change in C-peptide Area Under the Curve Measured by Mixed-meal Tolerance Test (MMTT) Between Group on GFD and Standard Gluten-containing Diet. | 1539 pmol*min/l | Standard Deviation 1255 |
| Conventional Diet | Change in C-peptide Area Under the Curve Measured by Mixed-meal Tolerance Test (MMTT) Between Group on GFD and Standard Gluten-containing Diet. | 1173 pmol*min/l | Standard Deviation 1006 |
p-value: <0.0595% CI: [-223, 633]Regression, Linear
Secondary
Changes in Immunological Parameters (FoxP3 Tregs, Th1 and Th17 Counts) at 12 Months Relative to Baseline at Month 1.
Time frame: Month 1 (baseline) - Month 12 (end of intervention)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gluten-free Diet | Changes in Immunological Parameters (FoxP3 Tregs, Th1 and Th17 Counts) at 12 Months Relative to Baseline at Month 1. | TEMRA cells at 12 months | 8 % of cells | Standard Deviation 2.2 |
| Gluten-free Diet | Changes in Immunological Parameters (FoxP3 Tregs, Th1 and Th17 Counts) at 12 Months Relative to Baseline at Month 1. | T-regulatory cells type 1 at 12 months | 1.02 % of cells | Standard Deviation 0.63 |
| Conventional Diet | Changes in Immunological Parameters (FoxP3 Tregs, Th1 and Th17 Counts) at 12 Months Relative to Baseline at Month 1. | TEMRA cells at 12 months | 12.5 % of cells | Standard Deviation 3.5 |
| Conventional Diet | Changes in Immunological Parameters (FoxP3 Tregs, Th1 and Th17 Counts) at 12 Months Relative to Baseline at Month 1. | T-regulatory cells type 1 at 12 months | 0.46 % of cells | Standard Deviation 0.16 |
p-value: <0.05t-test, 1 sided
Secondary
Changes in Mean HbA1c at 6 and 12 Months Relative to Baseline at Month 1.
Time frame: Month 1 (baseline) - Month 6 - Month 12 (end of intervention)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gluten-free Diet | Changes in Mean HbA1c at 6 and 12 Months Relative to Baseline at Month 1. | HbA1c at 6 months | 44.8 mmol/mol | Standard Deviation 6.3 |
| Gluten-free Diet | Changes in Mean HbA1c at 6 and 12 Months Relative to Baseline at Month 1. | HbA1c at 12 months | 44 mmol/mol | Standard Deviation 9.5 |
| Conventional Diet | Changes in Mean HbA1c at 6 and 12 Months Relative to Baseline at Month 1. | HbA1c at 6 months | 47.2 mmol/mol | Standard Deviation 8.3 |
| Conventional Diet | Changes in Mean HbA1c at 6 and 12 Months Relative to Baseline at Month 1. | HbA1c at 12 months | 52.2 mmol/mol | Standard Deviation 10.6 |
p-value: <0.0595% CI: [-14.1, -1.6]Regression, Linear
Secondary
Changes in Mean Insulin Dose at 6 and 12 Months Relative to Baseline at Month 1.
Time frame: Month 1 (baseline) - Month 6 - Month 12 (end of intervention)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gluten-free Diet | Changes in Mean Insulin Dose at 6 and 12 Months Relative to Baseline at Month 1. | Insulin dose at 6 months | 0.41 U/kg/day | Standard Deviation 0.17 |
| Gluten-free Diet | Changes in Mean Insulin Dose at 6 and 12 Months Relative to Baseline at Month 1. | Insulin dose at 12 months | 0.50 U/kg/day | Standard Deviation 0.22 |
| Conventional Diet | Changes in Mean Insulin Dose at 6 and 12 Months Relative to Baseline at Month 1. | Insulin dose at 6 months | 0.62 U/kg/day | Standard Deviation 0.23 |
| Conventional Diet | Changes in Mean Insulin Dose at 6 and 12 Months Relative to Baseline at Month 1. | Insulin dose at 12 months | 0.75 U/kg/day | Standard Deviation 0.34 |
p-value: <0.0595% CI: [-0.31, 0.01]Regression, Linear
Secondary
Differences in Fecal Microbiome Between Children on Normal Diet and Children on Gluten-free Diet Over the First Year of Diabetes Duration
Measures are shown as pooled values at all timepoints during the intervention period compared to control group throughout the same time-period.
Time frame: Month 1 (before intervention) - Pooled values throughout the intervention (months 3-12) - Month 15 (after intervention)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gluten-free Diet | Differences in Fecal Microbiome Between Children on Normal Diet and Children on Gluten-free Diet Over the First Year of Diabetes Duration | Bifidobacterium | 3.3 Percentage of microbes |
| Gluten-free Diet | Differences in Fecal Microbiome Between Children on Normal Diet and Children on Gluten-free Diet Over the First Year of Diabetes Duration | Roseburia | 3.2 Percentage of microbes |
| Gluten-free Diet | Differences in Fecal Microbiome Between Children on Normal Diet and Children on Gluten-free Diet Over the First Year of Diabetes Duration | Lachnospira | 1.01 Percentage of microbes |
| Conventional Diet | Differences in Fecal Microbiome Between Children on Normal Diet and Children on Gluten-free Diet Over the First Year of Diabetes Duration | Bifidobacterium | 8 Percentage of microbes |
| Conventional Diet | Differences in Fecal Microbiome Between Children on Normal Diet and Children on Gluten-free Diet Over the First Year of Diabetes Duration | Roseburia | 1.2 Percentage of microbes |
| Conventional Diet | Differences in Fecal Microbiome Between Children on Normal Diet and Children on Gluten-free Diet Over the First Year of Diabetes Duration | Lachnospira | 0.21 Percentage of microbes |
p-value: <0.05ANOVA